Since their original development by Professor Otto Bayer, polyurethanes have become widely used in a range of different applications, such as in the footwear, construction, textile and automotive industries. Of particular interest, however, is the use of polyurethanes in the medical product industry. In this field alone, the range of applications is extensive and includes, for example, artificial heart components, wound dressing products and catheters, to mention but a few. Further new areas of application are also under development, such as, for example, replacement joints and vertebrae. The biomedical field imposes particularly stringent requirements in general on any synthetic materials intended for inclusion in medical devices and polyurethanes are no exception. For example, the difficulties caused by build-up of deposits on polyurethane catheters, fatigue failure of heart valves and bio-decomposition are well known. Also, any medical devices intended for implantation must be free of potentially harmful substances that could leach from the implant in vivo. Although problems of this sort can be readily identified, the solutions are not always immediately obvious as there is usually a complex relationship between the surface chemistry and molecular structural features of the polymers, their morphology, the fabrication process and the device design. To date, such inter-relationships are not well understood and, in most instances, evaluation studies have been based on ill-defined commercial polymers. Whilst some efforts have been made to tailor materials for improved end-use properties and to gain an understanding of their properties, little attention seems to have been directed to the precision manufacture of quantities of materials for specific biomedical applications, which exhibit controlled and consistent bulk and surface properties.
Polyurethanes are generally synthesised by the reaction between a multifunctional isocyanate, a polyol and a chain extender, the isocyanate reacting with the polyol to form a low molecular weight pre-polymer, which is converted to a higher molecular weight polymer by chain extension or cross-linking with a chain extender. For some applications requiring low molecular weight polyurethanes, however, it may not be necessary to use a chain extender. For most applications, however, a bifunctional or polyfunctional chain extender will be used to effect chain extension or cross-linking, respectively. Moreover, it is possible to vary the order of reaction of the various components, for example, such that the isocyanate is first reacted with only a portion of the polyol or the chain extender so as to send cap the latter, prior to reaction with the remainder of the polyol or chain extender. A range of isocyanates, polyols and chain extenders are available commercially, with different chemical structures, molecular weights and functionalities. Most isocyanates are usually polyfunctional aromatic, aliphatic or alicyclic compounds. A variety of different polyols are available and include hydroxy-terminated esters, ethers or carbonate diols of varying molecular weights, with varying levels of hydrophobicity, hydrophilicity and backbone modifications. A number of chain extenders are available, which are typically low molecular weight polyols polythiols or amines of varying functionality. The choice of isocyanate, polyol and chain extender is determined by the final application. Other reagents can be added to form active chain-end groups or modify the bulk and surface properties for a specific application. Clearly, the number of possible combinations of isocyanate, polyol, chain extender and additional modifiers, and the number of different types of polyurethanes that can be produced from these, is considerable. In contrast to polymers such as, for example, polyethylene or polypropylene, therefore, the polyurethanes represent an entire family of materials, of widely differing characteristics. Moreover, a range of physical, mechanical and chemical properties can be attained by adjusting the ratio of isocyanate, polyol and chain extender. The polyol, being longer and more flexible, is commonly referred to as the soft segment, and the isocyanate and chain extender units are referred to as the hard segment. Therefore, a polyurethane with a high hard segment content will be relatively hard and rigid, whereas a polyurethane with a low hard segment content will be relatively soft and flexible. These hard and soft segments are immiscible, and phase segregation occurs forming soft and hard segment domains. When molten, the polyurethane is phase-mixed, that is, the soft segment is interspersed with hard segment and view. When cooled to a solid, phase segregation will begin, the rate at which this occurs being determined by time and temperature. Several commercially available polyurethanes require annealing after melt processing to increase the rate of phase segregation and to attain their required mechanical and physical properties. For polyurethane elastomers, the presence of these discreet hard segment domains dispersed within the soft segment matrix acts like a reinforcing filler and is primarily responsible for their good mechanical properties. Aqueous polyurethanes, which can be used to form reticulated coatings of the kind described in British Patent No. 2,331,717 that are suitable for application to medical devices and other medical products such as catheters or surgical gloves, can be manufactured by the selection of a suitably hydrophilic soft segment. The molecular weight of the pre-polymer formed by reacting the isocyanate with the polyol is ultimately limited by the viscosity of the pre-polymer solution, with higher molecular weight pre-polymers resulting in more viscous solutions. Chain extension is carried out in the water phase and an internal emulsifier (part of the polyurethane backbone) or an external emulsifier is used to aid dispersion. A co-solvent is usually added before chain extension to reduce the viscosity of the reaction mixture and to aid subsequent film forming during water evaporation. Up until now, though, it has not been possible to produce aqueous polyurethanes from very high molecular weight pre-polymers owing to the physical constraints associated with handling reaction mixtures of such high viscosity.
Conventional methods for making polyurethanes include both one step and two step processes. The one step method involves concurrent mixing of isocyanate, polyol and chain extender either in a batch reactor, when a solvent is employed, or in a mould, in the case of bulk polymerisation. Using a solvent enables much better mixing and reaction control. However, extra cost is incurred as the solvent must be recovered at the end of the process, whilst its subsequent disposal may well present environmental difficulties. The two step method involves the manufacture of a pre-polymer in a first step, usually from isocyanate and one or more polyols, and then, in a second step, chain extension with a stoichiometric amount of isocyanate, polyol or chain extender, depending on how pre-polymer synthesis was carried out. The two step approach can be carried out in solution or in bulk, the latter necessitating the use of an appropriate delivery and mixing means, such as, for example, reaction injection moulding equipment. Reaction injection moulding (RIM) methods were specifically developed for the direct manufacture of polyurethane products by bulk polymerization in moulds and such methods have been extensively reviewed (see, for example, P D Coated, G R Davies, R A Duckett, A F Johnson and I M Ward, Some Routes for Tailoring of Polymer Properties through Processing, Trans IChemE, Vol. 73, Part A, September, 1995). Most RIM systems comprise pumps that are capable of independently delivering an isocyanate and polyol stream through some form of mixing device directly into a mould, where reaction takes place to form the final object, such as, for example, a shoe sole. Impingement mixing at a molecular level is generally achieved by forcing the different reagent streams through a mix-head under high velocity and pressure, such that vigorous mixing occurs instantaneously. The main advantages of RIM methods are the precision with which it is possible to control the stoichiometry of the co-reagents and the high degree of mixing of the reagents that can be achieved during the mould filling process. There are many different designs of RIM machines, the principal variations depending on whether they are intended to be capable of handling reinforcing agents in the fluid streams (RRIM), pumping the reagents over a pre-placed reinforcement in a mould (SRIM), operating at high temperatures, or simply handling low viscosity non-reinforced fluids. The first three systems have pumps that operate at high pressures (typically 150-200 bar), whilst systems for handling low viscosity non-reinforced fluids have pumps which operate at much lower pressures. A further distinction can be drawn between machines that employ self-cleaning impingement mix-heads and those with simpler mechanical mixing devices, such as mechanical stirrers, which require the removal of polymer residues between injections or after a series of injections, using a solvent or an air purge. Mechanical mixing devices are normally only employed in low pressure systems, which are well suited to the manufacture of low modulus products, such as polyurethane foams, using chemical or physical blowing methods. RRIM and SRIM methods demand the use of lance pumps and are generally used in conjunction with sophisticated self-cleaning mix-heads. Such methods are particularly well-suited to the manufacture of large surface-area composite products for the automobile industry, such as, for example, car body panels. However, there are significant problems associated with the use of such methods for making small, complex shaped or thick section products, of the kind often required in biomedical applications. Consequently, RIM and other conventional batch process methods are of limited interest for the manufacture of polyurethane biomedical devices, which require products of exceptional quality and reproducibility. Polyurethanes can also be manufactured in a continuous manner in an appropriately designed extruder reactor by reactive extrusion (REX). Isocyanate and polyol streams are usually fed to the extruder in stoichiometric amounts, in order to achieve steady-state flow conditions. The extruder performs many functions, including mixing of reagents and delivery of the reacting mass to a suitable die, usually a strand die, which allows pelletisation of the product for subsequent use in injection moulding or further extrusion processes. In addition, the physical and chemical properties of the resultant polyurethanes can be modified in the extruder, the most common types of modification being: grafting, where a relatively unreactive basic polymer is reacted with low molecular weight reagents to increase its activity; reactive blending, where the basic polymer is blended with one or more secondary polymers to form new block or graft co-polymers; degradation, where the basic polymer is degraded in a controlled manner, to form lower molecular weight polymers of desired processing characteristics; functionalisation, where specific chemical groups are grafted on to the surface of the basic polymer, to improve or alter its polarity, reactivity or surface activity; and cross-linking or chain extension, where the basic polymer is reacted with cross-linking agents or chain extenders to increase its molecular weight or viscosity. Like RIM, conventional REX methods have also been used for the manufacture of polyurethanes for biomedical applications, but have been found to be less than ideal because they do not give rise to materials having sufficiently reproducible properties. This may be due to a number of different factors, such as inadequate control of reaction stoichiometry, imperfect mixing, or poor temperature control. With many REX processes, for example, it is common practice to blend the pelletised product in silos, in order to remove any instantaneous variability in the materials so obtained. When the polyurethanes of conventional processes are subjected to a post-polymerisation extrusion-pelletisation process, additional thermal and mechanical stresses can cause further changes to take place, such as, for example, degradation of the polymer, which may significantly influence its inherent properties. Indeed, post-polymerization processing of polurethanes will always impart the character of the processing method on the final product, whether it be an injection moulding, coating, or extrusion process. In general, though, processing conditions can be better controlled than polymer synthesis and, thus, the removal of variability in the polymer synthesis stage is of considerable importance. It is an object of the present invention, therefore, to overcome some of the aforementioned disadvantages by providing a process for manufacturing polyurethanes with a high degree of precision and reproducibility.